UDC

[616-097-053.1:616.34-008.87]:611.018.1

Authors

Dobrodeeva Liliya Konstantinovna, The Institute of Environmental Physiology, Ural Branch of the Russian Academy of Sciences (Arkhangelsk, Russia) 

Abstract

The paper evaluates the intensity of innate immunity responses in mucosa-associated lymphoid tissue to changes in the composition of microorganisms inhabiting mucous in healthy people and those with inflamed gut. It shows the age-related dynamics of the content of oncofetal antigens in the blood, with the rise of mucous glycoproteins in patients older than 60 years. We found that mucous glycoproteins accumulate in the blood serum in order to enhance the protective activity of the surface epithelium of the mucous membrane. The content and structure of mucosa-associated lymphoid tissue cells are reinforced by migrating neutrophil granulocytes, monocytes/macrophages, and natural killer cells. The highest activity of phagocytic protection by mucosa-associated lymphoid tissue cells was recorded in the gut, while the lowest phagocytic activity was found in the urinary system (p < 0.01). The exceeded threshold of physiological concentrations of symbionts and their metabolic products causes innate immunity response in the tissue of barrier organs. Further we showed that the levels of phagocytic activity, neutrophilic in particular, depend on microorganism concentrations on the surface of barrier organs and that their increased levels activate neutrophil granulocyte migration from the bloodstream, as well as chemotaxis, adhesion, degranulation, and engulfment. Enhanced secretory activity of neutrophils allows a paracrine community of cells to form in mucosa-associated tissue. In cases where innate immunity fails to cope with pathogenic microflora, this paracrine community initiates the development of specific responses of the adaptive immunity.

Keywords

cytokines, mucosa-associated lymphoid tissue, microflora, granulocytes, monocytes, lymphocytes, phagocytosis, microflora.

References

1. Bollinger R.R., Barbas A.S., Bush E.L., Lin S.S., Parker W.J. Biofilms in the Large Bowel Suggest an Apparent Function of the Human Vermiform Appendix. J. Theor. Biol., 2007, vol. 249(4), pp. 826–831. 
2. Johansson M.E.V., Phillipson M., Petersson J., Velcich A., Holm L., Hansson G.C. The Inner of the Two Muc2 Mucin-Dependent Mucus Layers in Colon Devoid of Bacteria. PNAS, 2008, vol. 105, no. 39, pp. 15064–15069. 
3. Johansson M.E.V., Holmen Larsson J.M., Hansson G.C. The Two Mucus Layers of Colon Are Organized by the MUC2 Mucin, Whereas the Outer Layer Is a Legislator of Host-Microbial Interaction. PNAS, 2011, vol. 108, suppl. 1, pp. 4659–4665. 
4. Bristow C.L., Lyford L.K., Stevens D.P., Flood P.M. Elastase Is a Constituent Product of T Cells. Biochem. Biolphys. Res. Commun., 1991, vol. 181, no. 1, pp. 232–236. 
5. Demaria S., Schwab R., Gottesman S.R., Buskin Y. Soluble Beta 2-Macroglobulin-Free Class I Heavy Chains Are Released from the Surface of Activated and Leukemia Cells by a Metalloprotease. J. Biol. Chem., 1994, vol. 269, no. 9, pp. 6689–6694. 
6. Hwang C., Gatanaga M., Granger G., Gatanaga T. Mechanism of Release of Soluble Forms of Tumor Necrosis Factor/Lymphotoxin Receptors by Phorbol Myristate Acetate-Stimulated Human THP-1 Cells in vitro. J. Immunol., 1993, vol. 151, no. 10, pp. 5631–5638. 
7. Lee G., Azadi P. Peptide Mapping and Glycoanalysis of Cancer Cell-Expressed Glycoproteins CA215 Recognized by RP215 Monoclonal Antibody. J. Carbohydr. Chem., 2012, vol. 31, no. 1, pp. 10–30. 
8. Pal’tsev A.I, Volozhanina A.G. Osobennosti adaptatsionno-kompensatornykh protsessov u patsientov pozhilogo vozrasta s gastroezofageal’noy reflyuksnoy bolezn’yu [Features of Adaptive-Compensatory Processes in Elderly Patients with Gastroesophageal Reflux Disease]. Sibirskiy konsilium, 2007, no. 7(62), pp. 223–224. 
9. Shimizu T., Kida Y., Kuwano K. Cytoadherence-Dependent Induction of Inflammatory Response by Mycoplasma pneumoniae. Immunology, 2011, vol. 133, no. 1, pp. 51–61. 
10. Macpherson A.J., Geuking M.B., MacCoy K.D. Homeland Security: IgA at the Frontiers of the Body. Trends Immunol., 2012, vol. 33(4), pp. 160–167. 
11. Mantis N.J., Rol N., Corthesy B. Secretory IgAs Complex Roles in Immunity and Mucosal Homeostasis in the Gut. Mucosal Immunol., 2011, vol. 4(6), pp. 603–611. 
12. He B., Xu W., Santini P.A., Polydorides A.D., Chiu A., Estrella J., Shan M., Chadburn A., Villanacci V., Plebani A., Knowles D.M., Rescigno M., Cerutti A. Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL. Immunity, 2007, vol. 26, pp. 812–826. 
13. Arvola M., Gustafsson E., Svensson L., Jansson L., Holmdahl R., Heyman B., Okabe M., Mattsson R. Immunoglobulin-Secreting Cells of Maternal Origin Can Be Detected in B Cell-Deficient Mice. Biol. Reprod., 2000, vol. 63, pp. 1817–1824. 
14. Balkwill F., Charles K.A., Mantovani A. Smoldering and Polarized Inflammation in the Initiation and Promotion of Malignant Disease. Cancer Cell, 2005, vol. 7, pp. 211–217. 
15. Borregaard N., Cowland J.B. Granules of the Human Neutrophilic Polymorphonuclear Leukocyte. Blood, 1997, vol. 89, no. 10, pp. 3502–3521. 
16. Butcher S.K., Chahal H., Nayak L., Sinclair A., Henriquez N.V., Sapey E., O’Mahony D., Lord J.M. Senescence in Innate Immune Responses: Reduced Neutrophil Phagocytic Capacity and CD16 Expression in Elderly Humans. J. Leukoc. Biol., 2001, vol. 70 (6), pp. 881–886. 
17. Aguilar-Ruiz S.R., Torres-Aguilar H., González-Domínguez É., Narváez J., González-Pérez G., Vargas- Ayala G., Meraz-Ríos M.A., García-Zepeda E.A., Sánchez-Torres C. Human CD16+ and CD16- Monocyte Subsets Display Unique Effector Properties in Inflammatory Conditions in vivo. J. Leukocyte Biol., 2011, vol. 90, no. 6, pp. 1119–1131. 
18. Grage-Griebenow E., Flad H.D., Ernst M., Bzowska M., Skrzeczyñska J., Pryjma J. Human MO Subsets as Defined by Expression of CD64 and CD16 Differ in Phagocytic Activity and Generation of Oxygen Intermediates. Immunobiology, 2000, vol. 202, no. 1, pp. 42–50. 
19. Belge K.U., Dayyani F., Horelt A., Siedlar M., Frankenberger M., Frankenberger B., Espevik T., Ziegler-Heitbrock L. The Proinflammatory CD14+CD16+DR++ Monocytes Are a Major Source of TNF. J. Immunol., 2002, vol. 168, no. 7, pp. 3536–3542. 
20. Sánchez-Torres C., García-Romo G.S., Cornejo-Cortés M.A., Rivas-Carvalho A., Sánchez-Schmitz G. CD16+ and CD16– Human Blood Monocyte Subsets Differentiate in vitro to Dendritic Cells with Different Abilities to Stimulate CD4+ T Cells. Int. Immunol., 2001, vol. 13, no. 12, pp. 1571–1581. 
21. Everett M.L., Palestrant D., Miller S.E., Randal Bollinger R., Parker W. Immune Exclusion and Immune Inclusion: A New Model of Host-Bacterial Interactions in the Gut. Clin. Appl. Immunol. Rev., 2004, vol. 4, pp. 321–332. 
22. Hill D.A., Artis D. Intestinal Bacteria and the Regulation of Immune Cell Homeostasis. Annu. Rev. Immunol., 2010, vol. 28, pp. 623–667. 
23. Turner J.R. Intestinal Mucosal Barrier Function in Heath and Disease. Nat. Rev. Immunol., 2007, vol. 9(11), pp. 799–809. 
24. Thiery J., Keefe D., Boulant S., Boucrot E., Walch M., Martinvalet D., Goping I.S., Bleackley R.C., Kirchhausen T., Lieberman J. Perforin Pores in the Endosomal Membrane Trigger the Release of Endocytosed Granzyme B into the Cytosol of Target Cells. Nat. Immunol., 2011, vol. 12, no. 8, pp. 770–777. 
25. Betts M.R., Brenchley J.M., Price D.A., De Rosa S.C., Douek D.C., Roederer M., Koup R.A. Sensitive and Viable Identification of Antigen-Specific CD8+ T Cells by a Flow Cytometric Assay for Degranulation. J. Immunol. Methods, 2003, vol. 281, no. 1–2, pp. 65–78. 
26. Casazza J.P., Betts M.R., Price D.A., Precopio M.L., Ruff L.E., Brenchley J.M., Hill B.J., Roederer M., Douek D.C., Koup R.A. Acquisition of Direct Antiviral Effector Functions by CMV-Specific CD4+ T Lymphocytes with Cellular Maturation. J. Exp. Med., 2006, vol. 203(13), pp. 2865–2877.